This is a multidisciplinary research program, employing innovative neurophysiological and computer analytical methods for the study of interrelated neurophysiological and pharmacological aspects of epilepsy. In the clinically oriented research, analysis of temporal variability and biorhythms figures prominently in the experimental design. Studies of patterns of clinical and electrical epileptic activity over time examine therapeutic response in a parametric design as a function of drug levels, clinical seizure incidence, ictal and itterictal EEG discharges, and background EEG changes. Neurobiological studies are addressed to the latent defects in both the intrinsic and extrinsic control systems that promote susceptibility to epileptic activity and its propagation. These studies include: the mechanisms of action of anticonvulsant and convulsant drugs on neural membranes, synapses, and intercellular communication; the nature and function of slow currents and their role in epileptogenesis; the mechanisms involved in secondary epileptogenesis; the function and elaboration of intracortical and extracortical inhibitory mechanisms; and a search for pleiotropic membrane defects in idiopathic epilepsy.